DCEG Lung Cancer Study

Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types genotyping 515,922 single nucleotide polymorphisms (SNPs) in 5,739 incident lung cancer cases and 5,848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from 10 additional studies for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication resulting in 3,333 adenocarcinomas (AD), 2,589 squamous cell carcinomas (SQ), and 1,418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT) on chromosome 5p15.33, was associated with risk of adenocarcinoma (OR=1.23, 95%CI=1.13-1.33, P=3.02x10-7), but not other histologic types (OR=1.01, P=0.84, and OR=1.00, P=0.93, for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR=1.24, 95%CI=1.17-1.31, P=3.74x10-14 for AD and OR=0.99, P=0.69 and OR=0.97, P=0.48, for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma. Note: The lung study dataset to be released to dbGaP and caBIG excludes 47 individuals from the PLCO cohort who consented to participate only in cancer research projects and 22 individuals because of updated QC. Thus, the released dataset is derived from 11517 subjects, 5699 cases and 5818 controls. After the updated QC, the dataset to be released to dbGaP and caBIG includes 506062 SNPs.]]>
Lung Cancer Genome-Wide Association Scan MethodsLung cancer cases were included based on a lung cancer diagnosis established on clinical criteria and confirmed by pathology reports from surgery, biopsy, or cytology samples in approximately 95% of cases and on clinical history and imaging for the remaining 5%. Tumor histology was coded according to the International Classification of Diseases for Oncology. Of the eligible subjects, in the original analysis, 183 were excluded for issues related to genotyping quality control and 337 subjects were excluded with incomplete phenotype data resulting in a final dataset of 5739 lung cancer cases and 5848 controls. After the further exclusion of 47 individuals because of informed consent issues and 22 individuals for QC reasons, the dataset released in dbGap and caBIG includes 5699 cases and 5818 controls. The subjects included in the original analysis as reported in Landi et al., AJHG 2009, by study: Cases Controls EAGLE 1920 1979 ATBC 1732 1271 PLCO 1390 1924 CSP-II 697 674 The subjects included in the dataset to be released in dbGaP and caBIG, by study, after further exclusions for informed consent and QC reasons: Cases Controls EAGLE 1917 1978 ATBC 1732 1270 PLCO 1355 1896 CSP-II 695 674 Further details of genotyping exclusions are provided in Supplemental Table 2 of the AJHG Report (Landi et al.)]]>
We conducted a GWAS in 5739 lung cancer cases and 5848 controls (National Cancer Institute [NCI] GWAS) to search for overall susceptibility variants and variants associated with specific histologic types and smoking status. We also conducted a meta-analysis of the NCI GWAS with summary data from ten additional studies, for a total of 13,300 primary lung cancer cases and 19,666 controls, all of European descent. Four of the ten studies provided information on histology for replication analyses; 3333 AD, 2589 SQ, and 1418 SC cases were analyzed overall. The 11,587 subjects in the NCI GWAS were drawn from one population-based case-control study and three cohort studies; specifically: the Environment and Genetics in Lung Cancer Etiology (EAGLE), a population-based case-control study including 2100 primary lung cancer cases and 2120 healthy controls enrolled in Italy between 2002 and 2005; the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), a randomized primary prevention trial including 29,133 male smokers enrolled in Finland between 1985 and 1993; the Prostate, Lung, Colon, Ovary Screening Trial (PLCO), a randomized trial including 150,000 individuals enrolled in ten U.S. study centers between 1992 and 2001; and the Cancer Prevention Study II Nutrition Cohort (CPS-II), including over 183,000 subjects enrolled by the American Cancer Society between 1992 and 2001 across all U.S. states. Analyses stratified by histology in the NCI GWAS included 1730 AD cases, 1400 SQ cases, 678 SC cases, and groups of other histological types or of mixed histologies. These studies were approved by the individual institutional review boards of each location, and each subject gave his or her informed consent for participation. In the PLCO study, 47 individuals gave permission to participate only in studies involving lung cancer, and thus have been excluded from the dataset released on dbGaP and caBIG.]]>